p16、p53和Ki-67蛋白在宫颈上皮内瘤变中的表达及意义

目的 探讨p16、p53和Ki-67蛋白在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)中的表达及临床意义.方法 采用免疫组化SP法检测正常子宫颈或炎性病变组织、CIN1～3中p16、p53和Ki-67蛋白的表达.结果 p16、p53和Ki-67蛋白在正常子宫颈或炎性病变中罕见表达,在CIN1～3组织中三者表达均较高,随CIN级别升高p16、p53和Ki-67表达增强,各组间表达差异有统计学意义(P<0.05).同时p16、p53和Ki-67三者阳性表达均可见分层现象,在CIN1中大部分阳性细胞位于子宫颈鳞状上皮的下1/3,在CIN2中多累及上皮下2/3,而CIN3则普遍超过上皮的下2/3或全层弥漫阳性,各组间差异具有统计学意义(P<0.05).结论 p16、p53和Ki-67蛋白表达均与子宫颈上皮内瘤变的病变进展密切相关,联合检测p16和Ki-67的抗原表达可作为CIN分级诊断的辅助方法,具有较好的应用价值.     

宫颈鳞状上皮内病变与EBP50、p16和Ki-67表达的相关性分析

目的:评价Ezrin-radixin-moesin结合磷酸化蛋白50(Ezrin-radixin-moesin binding phosphoprotein 50,EBP50)、p16和Ki-67在正常宫颈组织和宫颈鳞状上皮内病变(Squamous intraepithelial lesion,SIL)中的表达及临床意义.方法:选取2018年10月至2020年06月正常宫颈组织21例、SIL组织80例,采用免疫组化方法检查EBP50、p16和Ki-67表达水平,通过相关性检验分析EBP50与p16、Ki-67表达的相关性.结果:EBP50在正常宫颈组织中表达明显高于SIL(P=0.000);SIL中p16和Ki-67表达显著高于正常宫颈组织中的表达(P=0.000);高级别鳞状上皮内病变(High-grade squamous intraepithelial lesion,HSIL)EBP50表达强度比低级别鳞状上皮内病变(Low-grade squamous intraepithelial lesion,LSIL)降低(P=0.003);EBP50与p16或Ki-67的表达在SIL中呈负相关.结论:EBP50、p16和Ki-67的检测对SIL的病理诊断具有参考价值.EBP50表达的降低与宫颈病变的级别升高相关,EBP50可作为判断SIL分级的有效辅助手段.     

宫颈上皮内肿瘤及宫颈鳞状细胞癌组织中HPV16感染与hTERT、p21waf1和Ki67表达的关系及意义

目的探讨宫颈鳞状细胞癌(SCC)及宫颈上皮内肿瘤(CIN)组织中人乳头瘤病毒(HPV)16感染与端粒酶反转录蛋白(hTERT)、抑癌基因p21waf1和增生抗原Ki67表达的关系及其意义。方法在130例宫颈组织中利用组织芯片技术结合原位杂交技术检测HPV16感染及结合免疫组织化学技术检测hTERT、Ki67、p21waf1的表达。结果(1)HPV16杂交信号阳性率及hTERT、Ki67表达在CINⅡ～Ⅲ级、原位癌、浸润性鳞癌组织中都显著高于正常宫颈组织(P均<0.05),浸润癌也显著高于CIN(P均<0.05),CIN三级之间差异也具统计学意义(P均<0.05)。(2)p21waf1仅在浸润性鳞癌组织中的阳性率显著低于正常宫颈组织(P<0.05),其他组别之间差异无统计学意义(P均>0.05)。(3)HPV16感染及Ki67表达与hTERT表达均呈正相关(P<0.05,r=0.339;P<0.05,r=0.398);HPV16感染、hTERT及Ki67表达与p21waf1表达均呈负相关(P<0.05,r=0.337;P<0.05,r=0.248;P<0.05,r=0.446);HPV16感染与Ki67表达无相关性(P>0.05)。结论宫颈上皮内肿瘤及宫颈鳞状细胞癌组织中hTERT、p21waf1、Ki67表达的改变可能与HPV16感染有关,且互相作用,共同影响CIN的发展及宫颈鳞癌的发生。这些指标综合分析可能为阐明HPV16的恶性转化机制以及为提高宫颈鳞癌及其癌前病变诊断率提供参考依据。组织芯片技术是高效的研究基因及其表达产物的技术平台。     

p16ink4a与Ki-67用于人宫颈病变 辅助诊断的比较

目的对p16ink4a与Ki-67作为辅助诊断人宫颈病变的两种标记物进行比较。方法采用免疫组织化学方法,检测p16ink4a与Ki-67蛋白在42例人正常宫颈组织,21例人宫颈上皮内瘤样变(CIN)Ⅰ级、21例CINⅡ、36例CINⅢ组织中的表达,用等级相关方法分析p16ink4a、Ki-67表达水平与CIN等级之间的相关性。计算两种标记物的敏感性、特异性、阳性预测价值、阴性预测价值和约登指数。结果p16ink4a和Ki-67表达均与CIN等级呈正相关。p16ink4a检测人宫颈病变的敏感性为83.3%,特异性为90.5%,阳性预测值为94.2%,阴性预测值为74.5%,约登指数为0.738。Ki-67检测人宫颈病变的敏感性为98.7%,特异性为16.7%,阳性预测值为68.75%,阴性预测值为87.5%,约登指数为0.154。联合使用两种标记物的敏感性、特异性均为83.3%。结论Ki-67敏感性、阴性预测值高,但特异性差,适用于早期发现人宫颈病变。p16ink4a特异性、阳性预测值高,是辅助诊断人宫颈病变的较好指标。综合比较,p16ink4a优于Ki-67。     

宫颈上皮内瘤变中p16INK4A和Ki-67的表达

摘要：目的探讨p16^INK4A、Ki-67和HPV抗原表达及高危型HPV（HR—HPV）检测在宫颈上皮内瘤变（CIN）病理诊断中的意义。方法选取宫颈活检病理确诊为CIN的组织蜡块101例,重新切片,应用免疫组化两步法检测p16^INK4A、Ki-67和HPV抗原表达,并取正常宫颈组织50例进行对比研究。同时,应用第二代杂交捕获法对其中25例CIN组织样品进行HR—HPV检测。结果p16^INK4A蛋白表达水平在CINI、CINⅡ、CINⅢ级之间差异有非常显著性（P〈0．001）,其表达水平随着CIN级别的增高而增加,呈现良好的线性相关性（P〈0．001）;Ki-67蛋白表达阳性细胞多少与CIN分级之间无显著相关性（P〉0．05）,但其在宫颈鳞状上皮中的位置分布与CIN级别之间却有显著相关性（P〈0．05）;HPV抗原免疫组化染色阳性反应仅呈现于CIN鳞状上皮表层挖空细胞内,其阳性率在不同级别CIN之间的差异无统计学意义（P〉0．05）;HR—HPV在CINI、CINⅡ和CINⅢ级的检出率分别为81．8％、80．0％和100．0％,但其检出率在不同级别CIN之间差异也无显著性（P〉0．05）。结论p16^INK4A和Ki-67染色对CIN的病理诊断和分级具有一定诊断价值,对于CINI级形态结构不典型的病例,HR—HPV的检测结果对病理诊断有辅助意义。     

HPV E6/E7mRNA检测与P16/Ki-67免疫组化检测对宫颈CIN2级病变的筛查价值探究

目的:研究人乳头瘤病毒(Human papilloma virus,HPV)E6/E7mRNA与免疫组化抑癌基因P16/细胞增殖核抗原Ki-67 在宫颈上皮内瘤样病变(Cervical intraepithelial neoplasia,CIN)2 级病变筛查中的应用价值.方法:选取 2020 年 2 月至 2023 年 2 月期间本院收治的 92 例宫颈炎症及病变患者作为研究对象.根据病理检查结果,将CIN2 级患者纳入研究组(n=45),宫颈CIN1 级和宫颈炎患者纳入对照组(n=47).对比两组HPV E6/E7mRNA、P16/Ki-67 单独及联合检测阳性表达率差异,采用Logistic回归分析影响CIN2 诊断的危险因素,并采用受试者工作曲线分析 HPV E6/E7mRNA 与 P16/Ki-67 单独及联合检测在宫颈 CIN2 级病变筛查的价值.结果:研究组HPV E6/E7mRNA、P16/Ki-67单独检测阳性率、联合检测阳性率(82.22%,77.78%,84.44%)高于对照组(63.83%,48.94%,53.19%)(P＜0.05).Logistic回归分析显示HPV E6/E7mRNA、P16/Ki-67 是影响CIN2 诊断的危险因素(P＜0.05);HPV E6/E7mRNA、P16/Ki-67 联合检测CIN2 级病变的受试者工作特征曲线下面积为 0.688(95%CI:0.579～0.798),优于 HPV E6/E7mRNA、P16/Ki-67 单独预测[0.592(95%CI:0.476～0.708);0.634(95%CI:0.519～0.748)].联合检测的准确度、灵敏度、特异度(68.8%,84.4%,53.2%)均高于单独检测HPV E6/E7mRNA(59.2%,82.2%,36.2%)、P16/Ki-67(63.4%,77.8%,48.9%).结论:HPV E6/E7mRNA与P16/Ki-67 免疫组化检测在宫颈CIN2 级病变筛查中具有一定的应用价值,可以显著提高筛查宫颈CIN2 级病变的诊断效能.     

c-myc和p53蛋白在宫颈癌组织中的表达及临床意义

目的探讨c myc和p53蛋白在宫颈癌中表达的临床意义。方法采用免疫组化法检测51例正常宫颈、宫颈上皮内瘤样病变(CIN)和宫颈鳞癌中的c myc和p53蛋白的表达,并用TUNEL法检测细胞凋亡数。结果正常宫颈c myc和p53未见表达,宫颈鳞癌c myc和p53表达高于CIN(P<0.05)。宫颈鳞癌和CIN的TUNEL标记率均低于正常宫颈,宫颈鳞癌与CIN及正常组比较相差非常显著(P<0.01)。结论细胞凋亡可能与宫颈癌的形成过程有关,c myc和p53蛋白过度表达在宫颈癌的发生发展中起很重要的作用。     

宫颈上皮内瘤变及宫颈鳞癌中cyclin D1、Ki-67的表达及其意义

目的： 检测细胞周期素D1（cyclin D1）、增殖细胞核抗原（Ki-67）在人乳头瘤病毒（HPV）感染患者宫颈上皮内瘤样病变（CIN）及宫颈鳞癌中的表达及其相关性,研究其在CIN及宫颈鳞癌发生及发展过程中的作用。方法: 研究组HPV阳性病理确诊CINⅠ17例、CINⅡ19例、CINⅢ23例、宫颈鳞癌23例,对照组HPV阳性病理确诊柱状上皮异位22例。应用免疫组化S-P法检测宫颈病变组织中cyclin D1、Ki-67蛋白的表达,杂交捕获二代检测宫颈分泌物中HPV感染的情况。结果: (1)Cyclin D1在5组宫颈组织细胞的细胞核内均有表达,CINⅢ组、宫颈鳞癌组与对照组比较差异显著（P<0.05）,CINⅢ组、宫颈鳞癌组与CINⅠ组比较差异显著（P<0.05）,宫颈鳞癌组与CINⅡ组比较差异显著（P<0.05）。(2)Ki-67在5组宫颈组织细胞的细胞核内均有表达,对照组与CINⅢ组比较差异显著（P<0.05）,对照组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅠ组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅡ组与宫颈鳞癌组比较差异显著（P<0.05）。(3)Cyclin D1、Ki-67在CIN及宫颈鳞癌中的表达强度呈正相关关系 （P<0.05）。结论: Cyclin D1和Ki-67在CIN和宫颈鳞癌发生发展及细胞增殖活动中起一定的作用;两者在CIN和宫颈鳞癌的发生发展中可能发挥协同作用。     

子宫颈癌及癌前病变HPV16、Ki-67的表达及其相关性

目的对子宫颈癌及癌前病变中HPV感染和增殖细胞核抗原Ki-67表达情况进行研究。方法对45例子宫颈浸润性鳞状细胞癌、5例子宫颈腺癌、35例子宫颈上皮内瘤变（CIN）和5例正常宫颈组织采用免疫组化EnVision法进行HPV16和Ki-67表达的检测。结果HPV16阳性率为78．9％（71／90）,其中HPV16阳性率在子宫颈癌组织中为76．0％（38／50）,在CIN病变中为94．3％（33／35）,在正常子宫颈黏膜上皮组织中为阴性（0／5）。Ki-67阳性细胞在正常子宫颈、CIN和子宫颈癌组织中表达逐级增加,显示Ki-67表达程度与组织学类型有关。HPV和Ki-67在CIN和癌组织中的表达呈显著相关（P〈0．005）。结论瑞安地区子宫颈癌及癌前病变组织中存在HPV感染,HPV感染可能在子宫颈癌的发生、发展中起着重要作用。联合应用Ki-67与HPV可作为筛选子宫颈癌高危个体有价值的生物学标记。     

Bcl-2蛋白、Ki-67抗原、雌激素受体及孕激素受体在子宫腺肌病子宫内膜中的表达

目的 检测与分析细胞凋亡抑制因子(Bcl-2蛋白)、细胞核相关抗原(Ki-67抗原)、雌激素受体(ER)、孕激素受体(PR)在子宫腺肌病(AM)在位内膜、异位内膜和正常子宫内膜中的表达情况及相关性,探讨其在AM发病机制中的作用.方法 采用免疫组织化学PicTureTM二步法检测40例AM在位内膜、异位内膜及38例正常子宫内膜中Bcl-2蛋白、Ki-67抗原、ER、PR的表达情况.采用Spearman等级相关分析这些因素间表达的相关性.结果 (1)Bcl-2蛋白、Ki-67抗原在AM在位内膜和正常子宫内膜中表达有周期性变化,增生期高于分泌期(P＜0.05);而在AM异位内膜中表达无明显周期性变化.(2)Bcl-2蛋白、Ki-67抗原在3种内膜的表达情况:AM异位内膜＞AM在位内膜＞正常子宫内膜,差异有统计学意义(P＜0.05).(3)AM在位内膜、正常子宫内膜中Bcl-2蛋白、Ki-67抗原的表达与ER、PR的表达呈正相关(P＜0.05);AM异位内膜中Bcl-2蛋白、Ki-67抗原的表达与ER、PR的表达无相关.结论 AM在位、异位内膜中Bcl-2蛋白、Ki-67抗原的异常表达可能与AM的发生、发展有关.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

Postinfectious immunodeficiency and autoimmunity: pathogenic and clinical values and implications

Autoimmunity is still a mystery of clinical immunology and medicine as a whole. The etiology and pathogenesis of autoimmune disorders remain unclear and, thus, are assessed as a balance between hereditary predisposition, triggering factors and the appearance of autoantibodies and/or self-reactive T cells. Among the immunological armamentarium, molecular mimicry, based on self-reactive T- and B-cell activation by cross-reactive epitopes of infectious agents, is of special value. Hypotheses regarding the possible involvement of molecular mimicry in the development of postinfectious autoimmunity are currently very intriguing. They provide new approaches for identifying etiological agents that are associated with postinfectious autoimmunity, paired microbial- and tissue-linked epitopes targeted for autoimmune reaction determination, postinfectious autoimmunity pathogenesis recognition and specific prevention, and therapy for autoimmune disorder development.     

Beta-endorphin and drug-induced reward and reinforcement

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. beta-Endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.     

PTEN与信号转导及肿瘤

ＴＥＮ[1] (ｐｈｏｓｐｈａｔａｓｅａｎｄｔｅｎｓｉｎｈｏｍｏｌｏｇｙｄｅｌｅｔｅｄｏｎｃｈｒｏｍｏｓｏｍｅｔｅｎ)又名ＭＭＡＣ1 [2 ] (ｍｕｔａｔｅｄｉｎｍｕｔｉｐｌｙａｄａｎｃｅｄｃａｎｃｅｒ 1 )和ＴＥＰ1 [3 ] (ＴＧＦ -βｒｅｇｕｌａｔｅｄａｎｄｅｐｉｔｈｅｌｉａｌｃｅｌｌ -ｒｉｃｈｅｄｐｈｏｓｐｈａｔａｓｅ 1 ) (以下均称为ＰＴＥＮ) ,是 1 997年由 3个研究小组先后发现的一个具有双特异磷酸酶活性的抑癌基因。ＰＴＥＮ基因异常广泛存在于人类多种恶性肿瘤 ,如恶性神经胶质瘤、前列腺癌、子宫内膜癌、黑色素瘤等…     

Tobacco and alcohol and the risk of head and neck cancer

Summary We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.     

Muscle strength and serum testosterone,cortisol and SHBG concentrations in middle-aged and elderly men and women

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age-related declines in the maximal voluntary neuromuscular performance capacity in aging people.     

海洛因成瘾与学习记忆

海洛因成瘾是我国发病最高,危害最大的一种成瘾性疾病,而其中枢机制则是解决临床预防和治疗的关键,至今仍不清楚。既往工作表明,学习记忆功能在海洛因成瘾的中枢机制中居于重要的中心环节。本文在总结既往海洛因成瘾研究工作基础上联系学习记忆功能,试图从系统整合层次分析相关领域研究工作的不足和今后工作的发展方向。